We have demonstrated that the phorbol ester TPA is capable of causing induction of immunoglobulin synthesis in chronic lymphocytic leukemia cells (CLL). This induction involves increased levels of mRNA coding for the secretory form of IgM. Our goal in this study is to discern the mechanism(s) whereby TPA exerts its effects on these CLL cells. We have found that TPA induces IgM mRNA accumulation in a calcium-independent manner, but that TPA-induced secretion is calcium-dependent. Furthermore in normal B cells, induction of IgMmRNA by mitogen is calcium-independent while T cell supernatant stimulated IgM secretion is calcium-dependent. Thus, TPA can mimic both mitogen and T cell factors in their effects on B cell activitation. We have also identified a monoclonal antibody capable of inhibiting both TPA induced, T cell supernatant-induced and constitutive IgM secretion. This antibody may recognize a membrane protein which is phosphorylated during the course of IgM secretion.